EP1829538B1 - Preparation solide comprenant la coenzyme q10 reduite et procede pour la production de celle-ci - Google Patents

Preparation solide comprenant la coenzyme q10 reduite et procede pour la production de celle-ci Download PDF

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Publication number
EP1829538B1
EP1829538B1 EP05819588.4A EP05819588A EP1829538B1 EP 1829538 B1 EP1829538 B1 EP 1829538B1 EP 05819588 A EP05819588 A EP 05819588A EP 1829538 B1 EP1829538 B1 EP 1829538B1
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reduced coenzyme
solid preparation
weight
coating medium
oil
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EP1829538A1 (fr
EP1829538A4 (fr
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Tadao KANEKA CORPORATION Takasago Plant ONO
Takahiro KANEKA CORPORATION Takasago Plant UEDA
Shiro KANEKA CORPORATION Takasago Plant KITAMURA
Yasuyoshi KANEKA CORPORATION Takasago Plant UEDA
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Kaneka Corp
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Kaneka Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/06—Enzymes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/238—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin from seeds, e.g. locust bean gum or guar gum
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/25—Exudates, e.g. gum arabic, gum acacia, gum karaya or tragacanth
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/262—Cellulose; Derivatives thereof, e.g. ethers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/269—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of microbial origin, e.g. xanthan or dextran
    • A23L29/274—Pullulan
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A23P10/35—Encapsulation of particles, e.g. foodstuff additives with oils, lipids, monoglycerides or diglycerides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
    • A23P20/10—Coating with edible coatings, e.g. with oils or fats
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
    • A23P20/10—Coating with edible coatings, e.g. with oils or fats
    • A23P20/15—Apparatus or processes for coating with liquid or semi-liquid products
    • A23P20/18—Apparatus or processes for coating with liquid or semi-liquid products by spray-coating, fluidised-bed coating or coating by casting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/2873—Proteins, e.g. gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/288—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals

Definitions

  • This invention relates to a solid preparation containing reduced coenzyme Q 10 , a method for producing the same, a method for stabilizing a solid preparation containing reduced coenzyme Q 10 , and a method of handling the same.
  • Reduced coenzyme Q 10 shows higher oral absorbability as compared with oxidized coenzyme Q 10 and is a favorable compound suited for use in foods, functional nutritive foods, specific health foods, nutritional supplements, nutrients, animal drugs, drinks, feeds, cosmetics, medicines, remedies, preventive drugs, etc.
  • reduced coenzyme Q 10 is readily oxidized to oxidized coenzyme Q 10 by molecular oxygen, and it is still an important problem to stabilize reduced coenzyme Q 10 in processing the same in foods, functional nutritive foods, specific health foods, nutritional supplements, nutrients, animal drugs, drinks, feeds, cosmetics, medicines, remedies, preventive drugs, etc., or raw materials or compositions for the production thereof, and/or to stabilize the same in handling such products, raw materials or compositions after incorporation of the same.
  • WO01/052822 there are disclosed 1) a composition comprising an amount, effective in preventing reduced coenzyme Q 10 from being oxidized to oxidized coenzyme Q 10 , of a reducing agent and an amount, effective in dissolving the reduced coenzyme Q 10 and reducing agent, of a surfactant or a vegetable oil or a mixture of these, if necessary together with a solvent, 2) a composition for oral administration in the form of gelatin capsule or tablets as prepared from the above composition and, further, 3) a method for preparing the above composition containing reduced coenzyme Q 10 in situ by using oxidized coenzyme Q 10 and a reducing agent.
  • a method for stabilizing reduced coenzyme Q 10 which is characterized in that reduced coenzyme Q 10 is incorporated in a composition whose main component is a fat or oil (except for olive oil) and/or a polyol and which will not substantially interfere with the stabilization of reduced coenzyme Q 10 is disclosed as a method for protecting reduced coenzyme Q 10 against oxidation.
  • the above stabilization method may not enough to increase the stability of reduced coenzyme Q 10 to a satisfactory extent in some instances.
  • the above method uses a fat or oil and/or a surfactant and, therefore, the range of application thereof is limited.
  • WO 03/077895 A1 discloses a composition containing a coenzyme Q as the main component that improves the impaired glucose tolerance of diabetes patients.
  • JP 2003 026625 A discloses a solution of reduced coenzyme Q prepared by coating reduced coenzyme Q with liposome made of refined soybean lecithin.
  • coenzyme Q 10 and a method for handling the same to be used or practiced in the fields of foods, functional nutritive foods, specific health foods, nutritional supplements, nutrients, animal drugs, drinks, feeds, cosmetics, medicines, remedies, preventive drugs, etc.
  • the present inventors made intensive investigations in an attempt to accomplish the above object and, as a result, found that a solid preparation containing reduced coenzyme Q 10 coated with at least one coating medium selected from among oil-soluble coating media and water-soluble coating media can be protected in a surprisingly favorable manner against the oxidation, by molecular oxygen, of reduced coenzyme Q 10 in the solid preparation. Based on such finding, they have now completed the present invention.
  • enzyme Q 10 used herein means both of reduced one and oxidized one, and, in the case where there are both of them, the above term means the mixture as a whole.
  • the solid preparation of the disclosure which contains reduced coenzyme Q 10 comprises a solid composition containing reduced coenzyme Q 10 as coated with at least one coating medium selected from among oil-soluble coating media and water-soluble coating media.
  • the method of the disclosure for producing solid preparations containing reduced coenzyme Q 10 is characterized in that a solid composition containing reduced coenzyme Q 10 is coated with at least one coating medium selected from among oil-soluble coating media and water-soluble coating media.
  • the solid preparation of the invention which contains reduced coenzyme Q 10 may contain reduced coenzyme Q 10 alone or may further contain oxidized coenzyme Q 10 .
  • the proportion of reduced coenzyme Q 10 relative to the whole amount of coenzyme Q 10 is not particularly restricted but, from the viewpoint of performing the function of reduced coenzyme Q 10 markedly, it is, for example not lower than about 20% by weight, generally not lower than about 40% by weight, preferably not lower than about 60% by weight, more preferably not lower than about 80% by weight, still more preferably not lower than about 90% by weight, most preferably not lower than about 96% by weight.
  • the upper limit is, but is not limited to, 100% by weight and generally is not higher than about 99.9% by weight.
  • the weights of reduced coenzyme Q 10 and oxidized coenzyme Q 10 can be measured, for example, by the method described in the below-mentioned Examples.
  • reduced coenzyme Q 10 can be produced, for example, by preparing a mixture of oxidized coenzyme Q 10 and reduced coenzyme Q 10 by such a known method as synthesis, fermentation or extraction from a natural product and subjecting the mixture to chromatography for the concentration of the reduced coenzyme Q 10 fraction in the eluate.
  • the oxidized coenzyme Q 10 contained together with the reduced coenzyme Q 10 may be reduced with an ordinary reducing agent such as sodium borohydride or sodium dithionite, followed by concentration by chromatography.
  • Reduced coenzyme Q 10 can also be obtained by reacting an existing high purity grade of coenzyme Q 10 with such a reducing agent as mentioned above.
  • reduced coenzyme Q 10 is obtained by reducing oxidized coenzyme Q 10 such as an existing high purity grade of coenzyme Q 10 , or a mixture of oxidized coenzyme Q 10 and reduced coenzyme Q 10 with an ordinary reducing agent such as sodium dithionite, sodium borohydride or ascorbic acids.
  • reduced coenzyme Q 10 is obtained by reducing oxidized coenzyme Q 10 such as an existing high purity grade of coenzyme Q 10 , or a mixture of oxidized coenzyme Q 10 and reduced coenzyme Q 10 with ascorbic acids.
  • the solid composition prior to coating with at least one coating medium selected from among oil-soluble coating media and water-soluble coating media is not particularly restricted provided that it contains reduced coenzyme Q 10 .
  • reduced coenzyme Q 10 as such in the form of a powder or granules may be used as the solid composition for coating with a coating medium.
  • the solid composition into dosage forms suited for oral administration, for example powders, fine granules, granules, pills, tablets, hard capsules and soft capsules, according to the known methods for producing pharmaceutical preparations (e.g. the methods described in the Japanese Pharmacopoeia, 14th edition, General rules for preparations) using one or more additives accepted for use in foods, cosmetics and drugs.
  • Chewable tablets may be mentioned as a preferred tablet form.
  • the solid composition may also be prepared by admixing the above-mentioned additive(s) with a reduced coenzyme Q 10 -containing granular powder prepared by any of the generally employed methods of granulation (e.g. wet granulation methods such as spray granulation method, tumbling granulation method, extrusion granulation method and fluidized bed granulation method using a solution or dispersion containing water and/or an organic solvent; dry granulation methods such as fluidized bed granulation and tumbling granulation method using a powder binder) and compression molding the resulting mixture.
  • wet granulation methods such as spray granulation method, tumbling granulation method, extrusion granulation method and fluidized bed granulation method using a solution or dispersion containing water and/or an organic solvent
  • dry granulation methods such as fluidized bed granulation and tumbling granulation method using a powder binder
  • the additives mentioned above are not particularly restricted but include those accepted for use in foods, cosmetics and drugs. Those accepted for use in foods are particularly preferred.
  • the additives include excipients, disintegrating agents, lubricants, binders, coloring agents, agglomeration inhibitors, absorption promoters, dissolution aids, stabilizers, oils and fats, surfactants, and the like. It is of course possible to incorporate one or more active components other than reduced coenzyme Q 10 in the solid composition. These additives may be used singly or two or more of them may be used in combination.
  • excipients are not particularly restricted but include, for example, sucrose (purified sucrose, white soft sugar), lactose, glucose, starch, cornstarch, mannitol, crystalline cellulose, calcium phosphate, calcium sulfate and the like.
  • the disintegrating agents are not particularly restricted but include, for example, starch, agar, calcium citrate, calcium carbonate, sodium hydrogen carbonate, dextrin, crystalline cellulose, carboxymethylcellulose, tragacanth, alginic acid and the like.
  • the lubricants are not particularly restricted but include, for example, talc, magnesium stearate, polyethylene glycol, silica, hydrogenated oils and the like.
  • the binders are not particularly restricted but include, for example, ethylcellulose, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, tragacanth, shellac, gelatin, pullulan, gum arabic, polyvinylpyrrolidone, polyvinylalcohol, polyacrylic acid, polymethacrylic acid, sorbitol and the like.
  • the coloring agents are not particularly restricted but include, for example, titanium oxide, food colors, bengal colors, safflower colors, caramel colors, gardenia colors, tar colors, chlorophyll and the like.
  • the agglomeration inhibitors are not particularly restricted but include, for example, stearic acid, talc, light anhydrous silicic acid, hydrous silicon dioxide and the like.
  • the absorption promoters are not particularly restricted but include, for example, higher alcohols, higher fatty acids and the like.
  • the dissolution aids are not particularly restricted but include, for example, organic acids such as fumaric acid, succinic acid, malic acid and the like.
  • the stabilizers are not particularly restricted but include, for example, benzoic acid, sodium benzoate, ethyl parahydroxybenzoate, beeswax and the like.
  • oils and fats are not particularly restricted but may be, for example, natural oils and fats derived from animals or plants, synthetic oils and fats, or modified oils and fats. More preferred are those accepted for use in foods, cosmetics or drugs.
  • vegetable oils and fats there may be mentioned, for example, coconut oil, palm oil, palm kernel oil, linseed oil, camellia oil, brown rice germ oil, rapeseed oil, rice oil, peanut oil, corn oil, wheat germ oil, soybean oil, perillan oil, cotton seed oil, sunflower seed oil, kapok oil, evening primrose oil, shea butter, sal fat, cacao butter, sesame oil, safflower oil, olive oil and the like.
  • oils and fats there may be mentioned, for example, lard, milk fat, fish oils, beef tallow and the like.
  • modified oils and fats obtainable by the fractionation, hydrogenation, transesterificaiton, etc. of these natural oils and fats (e.g. hydrogenated oils). It is of course possible to use medium chain fatty acid triglycerides (MCTs). Mixtures of these may also be used.
  • medium chain fatty acid triglycerides there may be mentioned, for example, triglycerides whose fatty acid-derived moieties each contain 6 to 12 carbon atoms, preferably 8 to 12 carbon atoms.
  • oils and fats enumerated above vegetable oils and fats, synthetic oils and fats, and modified oils and fats, for example, are preferred from the easy handing and odor viewpoint.
  • vegetable oils and fats synthetic oils and fats, and modified oils and fats, for example, are preferred from the easy handing and odor viewpoint.
  • surfactants there may be mentioned, for example, fatty acid partial glycerides, propylene glycol fatty acid esters, phospholipids, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters, polyglycerol fatty acid esters and the like.
  • fatty acid partial glycerides there may be mentioned, for example, monoglycerides and diglycerides derived from fatty acids each containing 6 to 18 carbon atoms, preferably 6 to 12 carbon atoms.
  • propylene glycol fatty acid esters there may be mentioned, for example, monoesters and diesters derived from fatty acids each containing 6 to 18 carbon atoms, preferably 6 to 12 carbon atoms.
  • phospholipids there maybe mentioned, for example, egg yolk lecithin, purified soybean lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, dicetyl phosphate, stearylamine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositolamine, cardiolipin, ceramide phosphorylethanolamine, ceramide phosphorylglycerol, and mixtures of these, and the like.
  • egg yolk lecithin purified soybean lecithin
  • phosphatidylcholine phosphatidylethanolamine
  • phosphatidylserine phosphatidylserine
  • sphingomyelin dicetyl phosphate
  • dicetyl phosphate dicetyl phosphate
  • stearylamine phosphatidylglycerol
  • phosphatidic acid phosphati
  • sucrose fatty acid esters sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters and polyglycerol fatty acid esters
  • sucrose fatty acid esters sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters and polyglycerol fatty acid esters
  • sucrose fatty acid esters sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters and polyglycerol fatty acid esters
  • sorbitan fatty acid esters polyoxyethylenesorbitan fatty acid esters and polyglycerol fatty acid esters
  • fatty acids each containing 6 or more carbon atoms, preferably 8 or more carbon atoms.
  • the other active components are not particularly restricted provided that they are accepted for use in foods, cosmetics or drugs.
  • amino acids amino acids, vitamins, minerals, polyphenols, organic acids, sugars, peptides, proteins and the like.
  • the ones having an antioxidant activity for example, glutathione, L-cysteine, N-acetylcysteine, reduced ⁇ -lipoic acid, tocotrienol, vitamin E ( ⁇ -tocopherol) and ester derivatives thereof, vitamin C (ascorbic acid) and ester derivatives and salts thereof, erythorbic acid and ester derivatives and salts thereof, vitamin A and ester derivatives thereof, carotenoids, rutin, zeaxanthin, astaxanthin, lycopene, flavonoids, L-carnitine and pharmacologically acceptable salts thereof (e.g.
  • Preferred among these from the viewpoint of stabilization of reduced coenzyme Q 10 are carotenoids, astaxanthin, vitamin E and ester derivatives thereof, vitamin C and ester derivatives and salts thereof, and like antioxidants. It is of course possible to use two or more of the active components mentioned above in admixture.
  • the above-mentioned solid composition is coated using at least one coating medium selected from among oil-soluble coating media and water-soluble coating media so that reduced coenzyme Q 10 occurring in the solid composition may be inhibited from being oxidized into oxidized coenzyme Q 10 by molecular oxygen.
  • the coating is preferably other than an enteric coating, considering that the coating should be dissolved in the stomach or the like and coenzyme Q should be absorbed rapidly.
  • enteric coating so referred to herein, there may be mentioned compositions containing hypromellose phthalate, diethyl phthalate, polyethylene glycol or a like pharmacologically acceptable enteric coating component.
  • the oil-soluble coating media in the present invention are not particularly restricted provided that they are soluble in organic solvents other than water, for example the below-mentioned alcohols, ketones, halogenated hydrocarbons, hydrocarbons and the like.
  • the oil-soluble coating media are the ones having solubility (the weight of a solute (% by weight) relative to the weight of a saturated solution) in organic solvents of usually not less than 0.1% by weight, preferably not less than 0.5% by weight, more preferably not less than 1% by weight.
  • oil-soluble coating media there may be mentioned, for example, higher fatty acid sugar esters, shellac, cellulose derivatives, fatty acids and ester derivatives thereof, and oils and fats, zein and the like. From the viewpoint of stabilization of reduced coenzyme Q 10 , shellac, cellulose derivatives and zein are preferred, and shellac and zein are more preferred.
  • sucrose palmitate and the like which have solubility in organic solvents of within the above-mentioned ranges.
  • cellulose derivatives there may be mentioned, for example, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and sodium salts (sodium carboxymethylcellose, etc.) and calcium salts (calcium carboxymethylcellose, etc.) thereof, and the like, which have solubility in organic solvents of within the above-mentioned ranges.
  • fatty acids and ester derivatives thereof there may be mentioned, for example, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, behenic acid, and esters thereof (for example, methylesters, ethylesters thereof), and the like.
  • oils and fats there may be mentioned, for example, the above-mentioned oils and fats. From the viewpoint of maintaining the quality of the solid preparation, preferred are the oils and fats which are in solid state at ordinary temperature.
  • the water-soluble coating media in the present disclosure are not particularly restricted provided that they are soluble in water.
  • the water-soluble coating media are the ones having solubility (the weight of a solute (% by weight) relative to the weight of a saturated solution) in water of usually not less than 0.1% by weight, preferably not less than 0.5% by weight, more preferably not less than 1% by weight.
  • water-soluble coating media there may be mentioned, for example, gelatin, sugars, gum arabic, higher fatty acid sugar esters, tragacanth, pectin, pullulan, alginic acid, dried egg white, milk, curdlan, cellulose derivatives, casein, casein compounds, starch, yeast cell wall fractions and the like.
  • gelatin, sugars, gum arabic, pullulan, cellulose derivatives and yeast cell wall fractions are preferred, gelatin, sugars, cellulose derivatives and yeast cell wall fractions are more preferred, gelatin, cellulose derivatives and yeast cell wall fractions are still more preferred, and yeast cell wall fractions are particularly preferred.
  • sugars there may be mentioned monosaccharides and disaccharides such as sucrose (purified sucrose, white soft sugar), fructose, glucose, lactose and trehalose, sugar alcohols such as erythritol, mannitol, sorbitol, xylitol, maltitol, powdered reduced maltose syrup and reduced lactose, polysaccharides such as dextrin and maltodextrin, and the like.
  • sucrose purified sucrose, white soft sugar
  • fructose glucose
  • sugar alcohols such as erythritol, mannitol, sorbitol, xylitol, maltitol, powdered reduced maltose syrup and reduced lactose
  • polysaccharides such as dextrin and maltodextrin, and the like.
  • sucrose palmitate and the like which have solubility in water of within the above-mentioned ranges.
  • cellulose derivatives there may be mentioned, for example, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and sodium salts (sodium carboxymethylcellose, etc.) and calcium salts (calcium carboxymethylcellose, etc.) thereof, and the like, which have solubility in water of within the above-mentioned ranges.
  • solubility of the higher fatty acid sugar esters and the cellulose derivatives can be adjusted according to the species of esters, degree of polymerization and the like.
  • coating media oil-soluble coating media and water-soluble coating media accepted for use in foods are preferred.
  • coating media accepted for use in foods means arbitrary nontoxic coating media currently in use in the food industry.
  • Such coating media are not particularly restricted but include gelatin, sugars, gum arabic, pullulan, alginic acid, cellulose derivatives, yeast cell wall fractions, shellac, zein and the like.
  • water-soluble coating media are preferred from the in vivo disintegration and absorption viewpoint.
  • these coating media may be used singly or in the form of a mixture of two or more of them. Two or more coatings can also be made separately.
  • the process comprising coating the solid composition first with an oil-soluble coating medium and then further with a water-soluble coating medium.
  • the solid composition is preferably coated with shellac or ethylcellulose, for example, and then further coated with gelatin or a yeast cell wall fraction.
  • the process comprising coating the solid composition first with a water-soluble coating medium and then further with an oil-soluble coating medium.
  • the solid composition is preferably coated with gelatin, a yeast cell wall fraction or a cellulose derivative, for example, and then further coated with shellac, zein or the like . More preferably, the solid composition is coated with a yeast cell wall fraction and then further coated with shellac.
  • solid composition containing reduced coenzyme Q 10 can be coated with at least one coating medium selected from among such oil-soluble coating media and water-soluble coating media as mentioned above, it is of course possible to coat reduced coenzyme Q 10 alone directly or coat a solid composition prepared by any of the methods knows in the art, as mentioned above, to give a solid preparation containing reduced coenzyme Q 10 .
  • an auxiliary agent may be used, where necessary, for the purpose of forming suitable coatings, and the like.
  • the auxiliary agent is not particularly restricted provided that it is accepted for use in foods, cosmetics or drugs.
  • One accepted for use in foods for example a surfactant, plasticizer or coloring agent, is preferred, however.
  • the above-mentioned surfactants are not particularly restricted but include, for example, glycerol fatty acid esters, sucrose fatty acid esters, polysorbates and the like.
  • plasticizers are not particularly restricted but include, for example, polyethylene glycol, glycerol, triethyl citrate, propylene glycol, vegetable oils and fats, fish oils, animal oils and fats and the like.
  • coloring agents are not particularly restricted but include, for example, titanium oxide, food colors, bengal colors, safflower colors, caramel colors, gardenia colors, tar colors, chlorophyll and the like.
  • titanium oxide and caramel are preferred.
  • the process of coating with such a coating medium as mentioned above can be carried out in a per se known manner, for example in the manner of pan coating, dry coating, oscillating coating, fluidized bed coating or the like.
  • the coating medium may also contain water and/or an organic solvent which can dissolve the coating medium.
  • organic solvents are not particularly restricted in kind but include, for example, alcohols such as methanol, ethanol and 2-propanol; ketones such as acetone and methyl ethyl ketone; halogenated hydrocarbons such as chloroform and methylene chloride; hydrocarbons such as hexane, heptane and toluene; and the like.
  • Alcohols are particularly preferred, however.
  • Mixtures composed of two or more organic solvents, mixtures of water and an alcohol(s), mixtures of water and a ketone(s), and the like can of course be suitably used as well.
  • the temperature at which the above coating process is carried out is not particularly restricted but, from the viewpoint of stabilization of reduced coenzyme Q 10 and cost, the coating can be carried out generally at a temperature not higher than about 120°C, preferably not higher than about 100°C, more preferably not higher than about 80°C, still more preferably not higher than about 60°C, most preferably not higher than about 40°C.
  • the lower temperature limit is generally not lower than about 0°C, preferably not lower than about 10°C, more preferably not lower than about 15°C, still more preferably not lower than about 20°C, most preferably not lower than about 25°C.
  • the whole or a part of the production process is preferably carried out in a deoxidized atmosphere.
  • the whole production process is preferably carried out in a deoxidized atmosphere such as nitrogen gas, argon gas, helium gas or carbon dioxide.
  • the production method of the invention can be carried out at ordinary pressure, under increased pressure or under reduced pressure.
  • the weight proportion (%) of the at least one coating media selected from among oil-soluble coating media and water-soluble coating media relative to the weight (100% by weight) of the solid preparation containing reduced coenzyme Q 10 in the solid preparation obtained in the above manner is not particularly restricted but, from the cost viewpoint and the viewpoint of performing the function of the formed coatings, the upper limit value is generally not higher than about 99.9% by weight, preferably not higher than about 90% by weight, still more preferably not higher than about 80% by weight, still further preferably not higher than about 70% by weight.
  • the lower limit value is generally not lower than about 5% by weight, preferably not lower than about 10% by weight, more preferably not lower than about 15% by weight, still more preferably not lower than about 20% by weight, most preferably not lower than about 25% by weight.
  • the above-mentioned weight of the coating media is that determined after formulation.
  • the content of reduced coenzyme Q 10 in the solid preparation is not particularly restricted but, from the effectiveness, and the like, of reduced coenzyme Q 10 and easiness of formulation viewpoint, it is preferably 0.1 to 95% by weight, more preferably 1 to 90% by weight.
  • the solid preparation of the invention when preserved in the air at 40°C in a condition shielded from light for 30 days, shows a reduced coenzyme Q 10 retention percentage (percentage of the weight of reduced coenzyme Q 10 after preservation to the initial weight of reduced coenzyme Q 10 ) of not lower than about 50% by weight, preferably not lower than about 60% by weight, still more preferably not lower than about 70% by weight, still further preferably not lower than about 80% by weight, most preferably not lower than about 90% by weight.
  • the upper limit to the temperature at which the solid preparation of the invention is to be preserved is generally not higher than about 100°C, preferably not higher than about 80°C, still more preferably not higher than about 60°C, still further preferably not higher than about 40°C, most preferably not higher than about 20C.
  • the lower limit to that temperature is generally not lower than about -100°C, preferably not lower than about -80°C, still more preferably not lower than about -60°C, still further preferably not lower than about -40°C, most preferably not lower than about -20°C.
  • the humidity of the atmosphere in which the preparation is to be preserved is not particularly restricted but, from the viewpoint of stabilization of reduced coenzyme Q 10 , it is generally not higher than about 90%, preferably not higher than about 80%, more preferably not higher than about 75%, still more preferably not higher than about 60%, still further preferably not higher than about 40%, and the lower limit thereof is not lower than 0%, as expressed in terms of relative humidity.
  • the method for stabilizing a solid preparation containing reduced coenzyme Q 10 according to the disclosure is characterized in that a solid composition containing reduced coenzyme Q 10 is coated with at least one coating medium selected from among oil-soluble coating media and water-soluble coating media to thereby stabilize the resulting solid preparation containing reduced coenzyme Q 10 .
  • the method for handling a solid preparation containing reduced coenzyme Q 10 according to the invention is characterized in that the solid preparation containing reduced coenzyme Q 10 is placed in an environment adjusted to a relative humidity of not higher than 75%.
  • the stabilization indicates the inhibition of the oxidation of reduced coenzyme Q 10 to oxidized coenzyme Q 10 .
  • the handling is the exertion of an external action on something to cause the same to maintain or perform some or other function thereof.
  • Examples of the handling are not particularly restricted but may include discharging from the coating machine, packaging, packing, preservation, storage, transfer and the like.
  • a preferred handling consists in preservation.
  • the upper limit to the temperature at which the solid preparation containing reduced coenzyme Q 10 , of the invention, is to be preserved or handled in according to the method for stabilizing and the method for handling that preparation is generally not higher than about 100oC, preferably not higher than about 80oC, still more preferably not higher than about 60oC, still further preferably not higher than about 40oC, most preferably not higher than about 20oC.
  • the lower limit to that temperature is generally not lower than about -100oC, preferably not lower than about -80oC, still more preferably not lower than about -60°C, still further preferably not lower than about -40°C, most preferably not lower than about -20°C.
  • the solid preparation of the invention when preserved in the air at 40°C in a condition shielded from light for 30 days, shows a reduced coenzyme Q 10 retention percentage of not lower than about 50% by weight, preferably not lower than about 60% by weight, still more preferably not lower than about 70% by weight, still further preferably not lower than about 80% by weight, most preferably not lower than about 90% by weight.
  • the humidity in the preserving atmosphere is important and, by controlling that humidity, it becomes possible to markedly improve the stability of the solid preparation containing reduced coenzyme Q 10
  • the upper limit to the relative humidity is generally not higher than about 90%, preferably not higher than about 80%, more preferably not higher than about 75%, still more preferably not higher than about 60%, still further preferably not higher than about 40%, and, in such a controlled environment, the solid preparation containing reduced coenzyme Q 10 can be handled in a more stable condition.
  • the lower limit to the relative humidity is not lower than 0%.
  • the reduced coenzyme Q 10 retention percentage after 30 days of preservation in the air at 40°C in a condition shielded from light is not lower than about 80% by weight, preferably not lower than about 85% by weight, more preferably not lower than about 90% by weight, still more preferably not lower than about 95% by weight, most preferably not lower than about 97% by weight.
  • Such an environment with a controlled relative humidity can be given, for example, by dehumidification from the environment; introduction of a dehumidified gas (preferably a dry inert gas, though air may also be employed) into the environment; and the like.
  • a dehumidified gas preferably a dry inert gas, though air may also be employed
  • the method of dehumidification is not particularly restricted but the dehumidification may be accomplished by the freezing of moisture or the use of a dehumidifier or a desiccant (e. g. silica gel, calcium chloride, synthetic zeolite), and the like. It goes without saying that if an environment having a controlled relative humidity is given, the method for creating the same does not matter in any way.
  • the preservation and/or handling of the solid preparation is preferably carried out in a deoxidized atmosphere, as a matter of course.
  • a deoxidized atmosphere such as an inert gas, for example nitrogen gas, argon gas, helium gas, carbon dioxide or the like.
  • the solid preparation containing reduced coenzyme Q 10 as obtained according to the invention can be handled, for example packaged and packed, using a glass bottle, a plastic bottle, a plastic bag, an aluminum-laminated bag or the like.
  • a glass bottle for example packaging or packing
  • materials to be used in the above-mentioned handling for example packaging or packing, there may be mentioned glass, high-density polyethylene, medium-density polyethylene, low-density polyethylene, polyethylene terephthalate, polyvinyl alcohol, polypropylene, polyvinyl chloride, polyvinylidene chloride and like materials.
  • Metal e.g.
  • aluminum film-based materials manufactured by lamination with any of the above-mentioned grades of polyethylene or polyethylene terephthalate, for example, can also be suitably used.
  • a material relatively inferior in gas barrier performance and moistureproofing performance for example polyethylene
  • the packages/packs obtained can be enclosed, if necessary, in a steel drum, resin drum, fiber drum, corrugated fiberboard box or like container for transportation and/or storage. It is of course possible to enclose a desiccant such as silica gel, calcium chloride or a synthetic zeolite in such a container.
  • a desiccant such as silica gel, calcium chloride or a synthetic zeolite
  • reduced coenzyme Q 10 which is unstable in the air can be maintained very stably.
  • Crystals of oxidized coenzyme Q 10 (100 g) and 60 g of L-ascorbic acid were added to 1000 g of ethanol, and the reduction reaction was carried out with stirring at 78°C. After the lapse of 30 hours, the mixture was cooled to 50°C and, while maintaining that temperature, 400 g of ethanol and 100 g of water were added. The resulting ethanol solution was cooled to 2°C at a rate of 10°C/hour with stirring. The precipitate was washed in sequence with cold ethanol and cold water, and the wet crystals obtained were dried under reduced pressure to give 95 g of dry white crystals (yield after isolation: 95 mole %). All the procedural steps except for vacuum drying were carried out in a nitrogen atmosphere. The purity of the crystals obtained was 99.1%, and the weight proportion (%) of reduced coenzyme Q 10 was 99.0%.
  • the uncoated tablets containing reduced coenzyme Q 10 as obtained in Synthesis Example 2 were sprayed with a solution composed of 500 g of an aqueous solution of a yeast cell wall fraction (product of KIRIN BREWERY CO., LTD., YeastWrap(R)) and 4 g of glycerol, followed by drying.
  • the uncoated tablets containing reduced coenzyme Q 10 as obtained in Synthesis Example 2 were sprayed with a solution composed of 450 g of purified water and 50 g of gelatin (product of Nitta Gelatin Inc., APH-100), followed by drying.
  • the uncoated tablets containing reduced coenzyme Q 10 as obtained in Synthesis Example 2 were sprayed with a solution composed of 450 g of purified water and 50 g of hydroxypropylmethylcellulose (product of Shin-Etsu Chemical Co., Ltd., Metolose 90SH-04)), followed by drying.
  • the uncoated tablets containing reduced coenzyme Q 10 as obtained in Synthesis Example 2 were sprayed with an ethanol solution of shellac (product of GIFU SHELLAC), followed by drying.
  • shellac product of GIFU SHELLAC
  • the uncoated tablets containing reduced coenzyme Q 10 as obtained in Synthesis Example 2 were sprayed with an ethanol solution of shellac (product of GIFU SHELLAC), followed by drying.
  • the tablets thus provided with a moistureproofing coating were further sprayed with an aqueous solution composed of 44 g of purified water, 44 g of purified sucrose and 12 g of gum arabic (product of Ina Food Industry Co., Ltd., Gum Arabic A), followed by drying.
  • a reduced coenzyme Q 10 -containing solid preparation sugar-coated tablets coated with about 80 mg, per tablet, of purified sucrose and gum arabic.
  • the uncoated tablets containing reduced coenzyme Q 10 as obtained in Synthesis Example 2 were sprayed with a solution composed of 500 g of an aqueous solution of a yeast cell wall fraction (product of KIRIN BREWERY CO., LTD., YeastWrap (R)) and 4 g of glycerol, followed by drying.
  • a reduced coenzyme Q 10 -containing solid preparation coated with about 50 mg, per tablet, of the yeast cell wall fraction.
  • this solid preparation was sprayed with an ethanol solution of shellac (product of GIFU SHELLAC), followed by drying.
  • shellac product of GIFU SHELLAC
  • Reduced coenzyme Q 10 -containing granules were prepared by mixing the reduced coenzyme Q 10 crystals obtained in Synthesis Example 1, hydroxypropylcellulose, lactose and ethanol together according to the formulation shown below, stirring and drying the mixture. Those granules were sprayed with a solution composed of 500 g of an aqueous solution of a yeast cell wall fraction (product of KIRIN BREWERY CO., LTD., YeastWrap(R)) and 4 g of glycerol, followed by drying. Thus was produced a reduced coenzyme Q 10 -containing solid preparation (granules) coated with about 30 g of the yeast cell wall fraction per 70 g of the granules.
  • a yeast cell wall fraction product of KIRIN BREWERY CO., LTD., YeastWrap(R)
  • Magnesium stearate (1 part by weight per 100 parts by weight of the granules) was admixed with this solid preparation (granules) and the resulting mixed powder was tableted on a rotary tablet machine to give reduced coenzyme Q 10 -containing tablets each having a total weight of 200 mg and containing 30 mg of reduced coenzyme Q 10 .
  • Reduced coenzyme Q 10 crystal 20 weight parts Hydroxypropylcellulose 6 weight parts Lactose 73 weight parts Ethanol 50 weight parts
  • the reduced coenzyme Q 10 crystals obtained in Synthesis Example 1, crystalline cellulose (AVICEL(R)), cornstarch and purified sucrose were mixed up according to the formulation given below and, further, magnesium stearate (1 part by weight) was admixed with the mixture obtained, to give a mixed powder.
  • the particle size of the mixed powder obtained was adjusted by sifting, and the sieved powder was tableted on a rotary tablet machine to give chewable tablets each having a total weight of 500 mg and containing 100 mg of reduced coenzyme Q 10 .
  • the coated tablets produced in Examples 1 to 4 and 6 to 8 were preserved in the following adjusted environment: shielded from light, in the air, 40°C and relative humidity 60%. After 15 days and 30 days, the weight proportions (%) of reduced coenzyme Q 10 were determined by the above-mentioned HPLC analysis. The results are shown in Table 1. For comparison, the results obtained with the uncoated tables produced in Synthesis Example 2 as a control are also shown. In evaluating the results, reduced coenzyme Q 10 retention percentages of not lower than about 80% by weight after 30 days of preservation in the adjusted environment (shielded from light, in the air, 40°C, relative humidity 60%) were regarded as indicative of successful stabilization.
  • Table 1 Coating medium Weight proportion (%) of reduced coenzyme Q10 After 15 days After 30 days
  • Example 1 Yeast cell wall 100% 100%
  • Example 2 Gelatin 100% 100%
  • Example 3 Hydroxypropylmethylcellulose 94% 90%
  • Example 4 Shellac 97% 94%
  • Example 6 Yeast cell wall+Shellac 100% 100%
  • Example 7 Yeast cell wall 100% 100%
  • Example 8 Yeast cell wally+Shellac 100% 100% Control Uncoated tablets 67% 45%
  • Example 1 The coated tablets produced in Example 1 were preserved in the following adjusted environments: shielded from light, in the air, 40°C, relative humidity 10%, 40%, 60% and 75%. After 15 days and 30 days, the weight proportions (%) of reduced coenzyme Q 10 were determined by the above-mentioned HPLC analysis. The results are shown in Fig. 1 . In evaluating the results, reduced coenzyme Q 10 retention percentages of not lower than about 80% by weight after 30 days of preservation in the adjusted environment (shielded from light, in the air, 40°C, each of relative humidity) were regarded as indicative of successful stabilization.
  • Example 2 The coated tablets produced in Example 2 were preserved in the following adjusted environments: shielded from light, in the air, 40°C, relative humidity 10%, 40%, 60% and 75%. After 15 days and 30 days, the weight proportions (%) of reduced coenzyme Q 10 were determined by the above-mentioned HPLC analysis. The results are shown in Fig. 2 . In evaluating the results, reduced coenzyme Q 10 retention percentages of not lower than about 80% by weight after 30 days of preservation in the adjusted environment (shielded from light, in the air, 40°C, each of relative humidity) were regarded as indicative of successful stabilization.
  • reduced coenzyme Q 10 which is unstable in the air can be maintained very stably.

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Claims (18)

  1. Préparation solide contenant une co-enzyme Q10 réduite
    laquelle comprend une composition solide contenant une co-enzyme Q10 réduite revêtue avec au moins un milieu de revêtement soluble dans l'eau, lequel est au moins une espèce choisie dans le groupe constitué de fractions de parois cellulaires de gélatine et de levure.
  2. Préparation solide selon la revendication 1,
    dans laquelle la composition solide comprenant une co-enzyme Q10 réduite est revêtue avec un milieu de revêtement soluble dans l'eau de fractions de parois cellulaires de gélatine et/ou de levure et ensuite de plus avec un milieu de revêtement soluble dans l'huile.
  3. Préparation solide selon la revendication 1,
    dans laquelle le milieu de revêtement est celui accepté pour une utilisation dans des aliments.
  4. Préparation solide selon la revendication 2,
    dans laquelle le milieu de revêtement soluble dans l'huile utilisé est au moins une espèce choisie parmi le shellac et la zéine.
  5. Préparation solide selon la revendication 1,
    dans laquelle la masse de revêtement totale du milieu ou des milieux de revêtement n'est pas inférieure à 5 % en masse mais n'est pas supérieure à 99,9 % en masse par rapport à la masse de la préparation solide.
  6. Préparation solide selon la revendication 1,
    laquelle présente un pourcentage de rétention de co-enzyme Q10 réduite qui n'est pas inférieur à 50 % en masse après 30 jours de conservation dans l'air à 40°C dans un état protégé de la lumière.
  7. Procédé de production d'une préparation solide contenant une co-enzyme Q10 réduite,
    dans lequel une composition solide contenant une co-enzyme Q10 réduite est revêtue avec au moins un milieu de revêtement soluble dans l'eau qui est une espèce choisie dans le groupe constitué de fractions de parois cellulaires de gélatine et de levure.
  8. Procédé de production selon la revendication 7,
    dans lequel la composition solide contenant une co-enzyme Q10 réduite est revêtue avec un milieu de revêtement soluble dans l'eau de fractions de parois cellulaires de gélatine et/ou de levure et ensuite de plus avec un milieu de revêtement soluble dans l'eau.
  9. Procédé de production selon la revendication 7,
    dans lequel le milieu de revêtement est celui accepté pour une utilisation dans des aliments.
  10. Procédé de production selon la revendication 8,
    dans lequel le milieu de revêtement soluble dans l'huile utilisé est au moins une espèce choisie parmi le shellac et la zéine.
  11. Procédé de production selon la revendication 7,
    dans lequel le revêtement est réalisé à une température qui n'est pas inférieure à 0°C mais pas supérieure à 120°C.
  12. Procédé de stabilisation d'une préparation solide contenant une co-enzyme Q10 réduite,
    dans lequel une composition solide contenant une co-enzyme réduite Q10 est revêtue avec au moins un milieu de revêtement soluble dans l'eau, qui est une espèce choisie dans le groupe constitué de fractions de parois cellulaires de gélatine et de levure, pour stabiliser par-là la préparation solide résultante contenant une co-enzyme Q10 réduite.
  13. Procédé de stabilisation selon la revendication 12,
    dans lequel la composition solide contenant une co-enzyme Q10 réduite est revêtue avec un milieu de revêtement soluble dans l'eau de fractions de parois cellulaires de gélatine et/ou de levure et ensuite de plus avec un milieu de revêtement soluble dans l'eau.
  14. Procédé de stabilisation selon la revendication 12,
    dans lequel le milieu de revêtement est celui accepté pour une utilisation dans des aliments.
  15. Procédé de stabilisation selon la revendication 13,
    dans lequel le milieu de revêtement soluble dans l'huile utilisé est au moins une espèce choisie parmi le shellac et la zéine.
  16. Procédé de stabilisation selon la revendication 12,
    dans lequel le pourcentage de rétention de co-enzyme Q10 réduite n'est pas inférieur à 50 % en masse après 30 jours de conservation à l'air à 40°C dans un état protégé de la lumière.
  17. Procédé de manipulation d'une préparation solide contenant une co-enzyme Q10 réduite,
    dans lequel la préparation solide contenant une co-enzyme Q10 réduite selon la revendication 1 est placée dans un environnement ajusté à une humidité relative qui n'est pas supérieure à 75 %.
  18. Procédé de manipulation selon la revendication 17,
    dans lequel le pourcentage de rétention de co-enzyme Q10 réduite n'est pas inférieur à 80 % en masse après 30 jours de conservation dans l'air à 40°C dans un état protégé de la lumière.
EP05819588.4A 2004-12-24 2005-12-22 Preparation solide comprenant la coenzyme q10 reduite et procede pour la production de celle-ci Active EP1829538B1 (fr)

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JP5377304B2 (ja) * 2007-06-22 2013-12-25 株式会社カネカ 補酵素ｑ１０含有組成物
JP2009149584A (ja) * 2007-12-21 2009-07-09 Kaneka Corp 還元型補酵素ｑ１０含有粒子状組成物及びその製造方法
JP4954907B2 (ja) * 2008-01-18 2012-06-20 サントリーホールディングス株式会社 ゼリー入り飲料
CN101514148B (zh) * 2009-03-27 2015-05-13 玉溪健坤生物药业有限公司 一种还原型辅酶q10的制备方法
CN104119209B (zh) * 2013-04-25 2018-03-02 浙江医药股份有限公司新昌制药厂 一种还原型辅酶q10干粉及其组合物以及制备方法
US11896685B2 (en) 2018-10-31 2024-02-13 Amorepacific Corporation Core-shell network structure comprising biopolymer and composition comprising same
KR20210069344A (ko) 2019-12-03 2021-06-11 (주)아모레퍼시픽 바이오 폴리머를 포함하는 효능물질 전달체
WO2023120557A1 (fr) * 2021-12-24 2023-06-29 株式会社カネカ Corps emballé de coenzyme q10 réduite et son procédé de stockage
WO2023120552A1 (fr) * 2021-12-24 2023-06-29 株式会社カネカ Emballage et procédé de conservation pour la coenzyme q10 réduite
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EP1829538A1 (fr) 2007-09-05
CA2588925A1 (fr) 2006-07-20
JP5021319B2 (ja) 2012-09-05
RU2007128342A (ru) 2009-01-27
EP1829538A4 (fr) 2012-06-27
CN101087598A (zh) 2007-12-12
CN101087598B (zh) 2010-12-08
DK1829538T3 (en) 2016-05-02
WO2006075502A1 (fr) 2006-07-20
KR20070091680A (ko) 2007-09-11
AU2005324603A1 (en) 2006-07-20
ES2563929T3 (es) 2016-03-16
TW200635605A (en) 2006-10-16
JPWO2006075502A1 (ja) 2008-06-12

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